Brain macrophage surface marker expression with HIV-1 infection and drug abuse: a preliminary study
Paul Shapshak1, Renée V Stewart, Pura Rodriguez de la Vega
1Department of Psychiatry and Behavioral Sciences, Comprehensive Drug Research Center, University of Miami School of Medicine, FL 33136, USA. pshapsha@med.miami.edu
Goal:
To determine the heterogeneity of surface marker expression of macrophages in the temporal lobe of patients who died with AIDS who were also Drug Abusers (DAs). We studied the expression of macrophage surface markers CD11c, CD14, CD68, and HLA-DR and T cell surface markers CD4, and CD8.
Background:
The macrophage is the prime locus for HIV-1-associated pathology, is the most frequently infected cell in the brain, and has the highest virus load compared to other cells. We previously described the heterogeneity of macrophage surface marker expression and performed morphometric analysis in peripheral nerves of patients who died from AIDS compared to HIV-1 negative individuals. We showed that the HIV-related neuropathy in AIDS is a multifocal process. It is similarly important to determine the expression of macrophage surface markers in brain. Temporal lobe tissue was selected for this preliminary study because we previously found elevated HIV-1 proviral DNA load and inflammatory processes in this neuroanatomic location for subjects who died with AIDS. There is a high prevalence of Drug Abuse in Miami, Florida, associated with AIDS that may interactively affect HIV-associated pathology.
Methods:
Temporal lobe tissue was examined from 17 HIV-1-seropositive patients (4 with Drug Abuse and 13 without Drug Abuse) and 11 HIV-seronegative individuals (5 with Drug Abuse and 6 without Drug Abuse). Standard immunohistochemistry utilized alkaline phosphatase conjugate secondary antibody and fuchsin substrate.
Results:
We found that HIV-1 infection and the interaction of HIV-1 infection and Drug Abuse produced changes in macrophage surface marker expression. Macrophage surface markers, CD11c, CD14, CD68, and HLA-DR, and T-cell marker CD4 were increased with statistical significance due to HIV-1 infection (all p < .001) whereas CD8 remained unchanged. Changes due to Drug Abuse alone were not significant. Interaction of Drug Abuse and HIV-infected individuals showed increased expression of CD68 (p = .011), HLA-DR (p = .001), CD4 (p = .027), and CD8 (p = .016).
Conclusion:
Drug Abuse and HIV-1 infection are factors that differentially and interactively result in multiple macrophages surface marker effects. In HIV-1 infected individuals, Drug Abuse stimulates surface marker expression. Since brain macrophage surface makers do not change uniformly as a result of Drug Abuse and HIV infection, these cells may be heterogeneous and contain sub-types (sub-sets). It remains to be determined which macrophage sub-types may be most pathognomic for pathology.
Insights
HIV-1 infection and drug abuse significantly alter macrophage surface markers in the brain. These factors interact, suggesting diverse macrophage subtypes may contribute to AIDS-related brain pathology.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Cell Biology
Background:
- Macrophages are central to HIV-1 neuropathology and are the most infected brain cells.
- Previous studies indicated heterogeneous macrophage surface marker expression in peripheral nerves of AIDS patients.
- Temporal lobe HIV-1 DNA load and inflammation are elevated in AIDS patients, making it a key area for study.
Purpose of the Study:
- To investigate the heterogeneity of macrophage surface marker expression in the temporal lobe of patients with AIDS, considering drug abuse.
- To analyze the expression of CD11c, CD14, CD68, HLA-DR (macrophage markers), and CD4, CD8 (T cell markers).
Main Methods:
- Examined temporal lobe tissue from 17 HIV-1-seropositive and 11 HIV-seronegative individuals.
- Included subgroups with and without a history of drug abuse.
- Utilized immunohistochemistry with alkaline phosphatase conjugate and fuchsin substrate.
Main Results:
- HIV-1 infection significantly increased CD11c, CD14, CD68, HLA-DR, and CD4 expression (p < .001), while CD8 remained unchanged.
- Drug abuse alone did not significantly alter marker expression.
- The interaction of drug abuse and HIV-1 infection elevated CD68, HLA-DR, CD4, and CD8 expression (p ≤ .027).
Conclusions:
- HIV-1 infection and drug abuse interact to influence macrophage surface marker expression differentially.
- Drug abuse appears to stimulate surface marker expression in HIV-1 infected individuals.
- Non-uniform changes suggest macrophage heterogeneity in the brain, with potential implications for pathology.
